[MIM 307 030]

(hyperglycerolemia, pseudohypertriglyceridemia)

Very rare. X-linked transmission of a mutation of the GK gene (Xp21).

Due to the contiguity of the genes on the X chromosome, this anomaly is often associated, in case of deletion of Xp21, with other pathologies as Duchenne's myopathy (DMD gene), adrenal failure by hypoplasia of the adrenals (DAX1 gene) or, more rarely, to a deficiency in ornithine carbamyl transferase (see this term).

This enzyme catalyzes the phosphorylation of exogenous glycerol into glycerol-3-phosphate at the level of the liver and kidney. Glycerol-3-phosphate can then be integrated in the gluconeogenesis, the esterification of fatty acids or be eliminated as CO2 (little in humans). It also seems that competition between hexokinase and glycerol kinase at the level of the outer mitochondrial membrane plays an important role in the regulation of lipids and carbohydrates. In normal conditions, the plasmatic level of free glycerol is below 0.15 mmol/L. It can be increased in case of cardiac dysrhthmias, unstable diabetes type 2 or some treatments such as heparinotherapy.

Hyperglycerolemia can produce, at varying degree, vomiting, lethargy, hypoglycemic coma and convulsions.

Three forms are distinguished:

-        infantile or complex glycerolkinase deficiency: in presence of a Xp21 deletion [MIM 300 679]. It manifests itself with neonatal hypoglycemia, hypotonia or acute adrenal failure. Facial dymorphim is present: hypertelorism, alternating strabism, rounded palpebral fissures, wide flattened earlobes

-        juvenile: without myopathy nor adrenal insufficiency; variable presentation: hypoglycemic coma or convulsions, during or  after an infection or exercize (catabolic stress); seizures risk disappears in adulthood because the brain glucose needs become proportionately lower.

-        adult: often asymptomatic, unexplained hypoglycemic or moderately hyperglycemic episodes; most often, incidental finding  of "pseudohypertriglyceridemia" that is in fact hyperglycerolemia (laboratory measurement artefact).

Treatment: symptomatic. Poor-fat diet to avoid the lethargy and vomiting associated with hyperglycerolemia.

Anesthetic implications: 

short preoperative fasting period or glucose-containing infusion once the preoperative fasting is started (risk of hypoglycemia). Avoid the use of continuous infusion of propofol as its excipient contains glycerol.

In case of congenital adrenal insufficiency, substitutive opotherapy.

In case of Duchenne myopathy, avoid halogenated agents and succinylcholine.

References:

-         Sargent CA, Kidd A, Moore S, Dean J, Besley GTN, Affara NA. 
Five cases of isolated glycerol kinase deficiency, including two families: failure to find genotype/phenotype correlation. 
J Med Genet 2000; 37: 434-41.

-        Van Obbergh LJ, Corteel J, Papadopoulos J, Aunac S.
Anesthesia for a child suffering from a deletion in the Xp21 loci resulting in Duchenne disease, glycerol kinase deficiency, and congenital adrenal hypoplasia.
Pediatr Anesth 2011; 21:1085-7.

-        Hellerud C, Wrammer N, Erikson A, Johansson A et al.
Glycerol kinase deficiency: follow-up during 20 years, genetics, biochemistry and prognosis.
Acta Paediatr 2004; 93: 911-21.

-        Scheurle A, Greenberg F, McCabe ERB.
Dysmorphic features in patients with complex glycerol kinase deficiency.
J Pediatr 1995; 126: 764-7.

-        Sehgal A, Stack J.
Complex glycerol kinase deficiency: an X-linked disorder associated with adrenal hypoplasia congenita.
Indian J Pediatr 2005; 72: 67-9.

-        Montoya-Williams D, Mowitz M.
Cholestasis and hepatic iron deposition in an infant with complex glycerol-kinase deficiency.
Pediatrics 2017; 140: e20161479

-        Backes JM, Dayspring TD, Hoefner DM, Contois JH et al.
Identifying pseudohypertriglyceridemia in clinical practice. 
Clinical Lipidology 2014;  9: 625-41

-        Rossell  B, Godart J, Petyt C, Veyckemans F.
Complex Glycerol Kinase deficiency (Xp21 Deletion syndrome): a case report of a contiguous gene disorder necessitating creative anesthetic planning.
A &A Practice 2020; 14: in press

Updated: September 2020